If breakthroughs take time, how can research help families today?

Recently, someone posed a question that made me think hard about the immediate relevance of our research to those affected by autism. I had been explaining Autism Speaks’ new focus on developing medicines that, one day, will target autism’s core symptoms in ways that reduce disabilities and improve learning abilities. Someone commented that this would likely take years to accomplish. I had to agree. His follow-up question: So, how does research help families today?

For the answer, I found myself thinking about how the Cystic Fibrosis Foundation faced this same question decades ago. Like Autism Speaks, the Cystic Fibrosis Foundation was grappling with a disorder in its medical infancy. Cystic fibrosis was defined as a medical condition in 1938. The Foundation followed in 1955. At that time, the median age of survival for those affected by the disorder was just ten years.

The leadership of the Cystic Fibrosis Foundation knew they were grappling with a complex disorder that would take years to fully understand. So they developed parallel research efforts. One focused on the immediate development of improved diagnosis and treatments that could ease symptoms. The other focused on basic science with the goal of ultimately revolutionizing treatment with therapies that target the disorder’s root causes.

Their short-term efforts included support for a network of clinical care and research centers, a patient registry and studies that focused on improving treatment of chronic symptoms and associated medical conditions. Within a relatively short time, diagnostic methods improved and physicians began adopting new gold-standard practices, including new methods for fighting lung infections and improving lung function – all made possible through research that the Cystic Fibrosis Foundation helped support. The median age of survival jumped from 10 years to 37 years!

Meanwhile, long-term research efforts focused on understanding the causes and biology of cystic fibrosis. In 1989, scientists made major breakthroughs in genetic understanding. This, in turn, led to tremendous insights into the disorder’s underlying biology. Then, just last week, the FDA approved the first drug to treat the underlying cause of cystic fibrosis, rather than its symptoms. One doctor described how his patient was able to “shovel snow for the first time.” Not coincidentally, the Cystic Fibrosis Foundation had contributed millions of dollars to the development of this drug (Kalydeco). Its early funding had been essential to convince drug companies to make the larger financial investment needed to bring any successful drug to market. In the process, the foundation negotiated a deal to earn drug royalties, which will now be reinvested in further research advancements. Just as exciting, other “disease-modifying” cystic fibrosis drugs are moving through the research pipeline.

This is the same strategy that Autism Speaks is taking with investments in both research that improves quality of life in the short term and longer-term research that promises to transform how autism is treated.

Here are just a few examples of funded research projects with the potential to improve quality of life in the near future:

Validation of questionnaires that pediatricians can use to screen babies for ASD and, so, offer earlier intervention that will improve outcomes

Biomarkers (e.g. immune alterations) that could identify infants at risk for ASD

Development of effective early interventions for babies before the full syndrome develops

Support of technological inventions to enhance communication in nonverbal persons

Development of physician guidelines for assessment and treatment of medical conditions associated with ASD

Development of more effective treatments for associated conditions, including sleep disturbances, GI disorders, seizures and anxiety

Development of interventions to improve employment success and relationship skills in adults

Development of cognitive rehabilitation interventions for adults

Even as we support the development of these improved services, we are also investing in research that can identify the most effective ways to broadly implement new gold-standard practices to produce positive changes in community healthcare, education and support services for all persons who struggle with autism. This type of “dissemination research” also tells us how to best target limited resources.

Meanwhile, our long-term investments are advancing the understanding of autism’s underlying biology and the genetic and environmental factors that contribute to its development. These investments are exploring the role of the immune system, brain signaling pathways and the GI system, among other topics. Over the last five years, tremendous progress in these areas has advanced research to the point where we are now collaborating with industry to develop novel drugs with the potential to ease severe and disabling core symptoms – in adults as well as children. Fortunately, the tools we have available today will make drug discovery and development much faster than before.

Connecting the dotsAt Autism Speaks, the research we fund interconnects with all parts of our mission, including awareness, advocacy and family services. Our awareness campaign, for example, is shaped by research that has revealed great disparities in access to services by communities such as ethnic-minority and low-income families.

Our advocacy of insurance reform, in turn, critically depends on research that demonstrates how early intervention improves outcomes. Research also plays a critical role in bolstering our advocacy for adolescents and adults. For example, a recent study demonstrated that adults with ASD face greater challenges in employment and social participation than do adults with other common disabilities. More importantly, this same study suggests that providing transition services immediately after high school is the most cost effective way to improve outcomes. We can use this information to advocate for improved services during the transition from high school to adulthood. Other currently funded studies promise to help us advance insurance reform to assure coverage of other interventions with proven benefits for school-age children and adults.

Similarly, Autism Speaks is funding research aimed at determining the real-world effects of proposed changes in the diagnostic criteria for autism. Will these new criteria exclude people previously diagnosed with ASD? Will they affect access to vital services? These answers will be crucial to our ability to advocate for any necessary changes in the proposed criteria.

While we see our research improving lives now, we remain committed to our long-term goals of revolutionizing treatment of ASD. I know in my heart that someday we will be making the kind of breathtaking announcement that we heard from the Cystic Fibrosis Foundation last week. The day is coming. In the meantime, we will ensure that our scientific mission remains relevant to our families today.

Thank you for your post, Dr Dawson.
However, living outside USA, I have to be skeptic. Not only gastro, sleep and other neurological problems are being faced by children, teens and adults diagnosed with ASD around the world, but also nutritional, toxicological, of mito dysfunction , immune, autoimmune, bacterial , fungal, viral and parasitic conditions. And these conditions remain untested, undiagnosed and untreated due to the lack of properly developed mainstraimed protocols and information developed to test, diagnose and treat them- beyond the causal inferences- available to peditricians and other doctors. Best guidelines for ASD do not include them.
Without strong efforts in the development of these improved protocols, whose fragments and parts are partially published, without the analysis of many anecdotic evidences that remain unanalyzed and not systematized, without the consideration of the case and the case series, I have to be skeptic about the time periods taken to develop properly these protocols- especially due to the challenges that families like mine face today.

This gave me a laugh. So essentially If we donate lots of money the way cystic fibrosis did, then the drug companies can come up with a pill that solves our recesive genetic disorder! Which i’m assuming we will have to pay for the pill after its devolped as well?

Wait,isn’t autism classified as a neurological disorder? And further more, isn’t comparing the two, one which effects the lungs, pancreas, liver and intestine vs one that effects neurotransmitters, and brain process’s a little bit of a reach?

Have you not been reading the studies that have been released? Anti-Depressents cause up to 3.8 times the rate autistic births? SSRI’s are causing suicide? To hear that your comfort to parents who suffer with autism is that “we will have a magic pill out when its done, and if you donate it will be done faster” is offensive, and this is from someone who actually has autism. Perhaps a better answer would be to explain to them programs that help learn how to control sensory overload, or programs exploring new ways of communication and teach with autistic’s are more likely to produce useable results in the next few years.

Another major immediate benefit of research can be the identification of a specific underlying genetic cause in individual patients. This can: (i) aid in acceptance of the condition by identifying a specific biological cause, (ii) point patients or parents towards support groups now emerging for specific genetic lesions (e.g., http://www.rarechromo.org/html/home.asp), (iii), provide immediately useful information regarding genetic risk to siblings, and (iv) in some cases indicate a specific prognosis. Eventually it may indicate an expected profile of responsiveness to various therapies.

In a second reading, I have to respectfully disagree considering the comparison of cystic fibrosis and ASD.
CF is caused by a mutation in the gene cystic fibrosis transmembrane conductance regulator (CFTR),found at the q31.2 locus of chromosome 7. There are hundreds of mutations of this gene and a tremendous amount of information of importance of individual mutations and presentation of CF.
G551D is found about 4-5% of cases of cystic fibrosis, and Kalydeco is effective (and approved by the U.S. Food and Drug Administration) only for cystic fibrosis with that mutation- near 1200 people in USA-, even when researchers hope that help other patients. Is this information correct?
The prognosis of FC is many times related to the kind of presentation, from medical literature, and the kind of medical problems related.
Now, I wonder
1-with the heterogeneity of ASD diagnosis, what group of genetic mutations are thought that could be helped such as it happens in the case of CF? and
2-what is the plan for the near 80-90 % of people diagnosed with ASD with no known specific genetic mutation to correlate with their symptoms?
and what is the role of the CMPs more and more cited in the open literature?
Thank you in advance

Evidence reported in the medical literature decades ago may be as important as any future breakthroughs. I will continue to point this out. (1) Autism is associated with many etiological factors, one of which is anoxia during childbirth. (2) In experiments with monkeys, ischemic injury of the brainstem auditory pathway was prominent. (3) Nuclei in the brainstem auditory pathway have greater blood flow than any other area of the brain, thus are more exposed to any toxic substance in the circulation. (4) The high blood flow also supports higher aerobic metabolism than in any other area of the brain. (5) Impairment of function in the auditory system will interfere with normal language development. (6) In monkeys subjected to asphyxia at birth, maturation of the brain did not progress normally.

I am the mother of a four and a half year old son that was diagnosed this past July. I am still feeling my way around and I don’t have the scientific knowledge that others that have posted seem to have.

I just have a question as a mother still grappling with guilt, you mentioned that one of the research projects was the development of effective early interventions for babies before the full syndrome develops. Does that mean that had my son received earlier intervention that we could have addressed the syndrome and today he would not be Autistic?

Melanie, please don’t be too hard on yourself. There is wondefull help out there in the ASD community. Wonderful books of encouragement, great local groups that offer support in what you are dealing with right now. I too have a child on the spectrum, and I can tell you support is crucial. One example of that support is the Autism Asperger’s Digest (http://autismdigest.com/). They have Temple Grandin and other wonderful columnist writing some amazing articles about life in the trenches with a child on the spectrum. They share their defeats along with triumphs. Might be worth looking into along with surrounding yourself with hope and support.

Ms.Dawson, I think you’re missing the obvious venues. It is high time autism was recast as an organic syndrome rather than a behavioral disorder, and research agendas and standard of care revised accordingly. In my opinion, AS is missing very significant areas of advocacy and research. There are 1M+ children who are already affected, some of whom may never fully recover – they need answers now.

Let me explain.

1) WE NEED MORE RESEARCH ON AUTISM PATHOPHYSIOLOGY: For many diseases where causality is unknown, you treat the pathophysiology – there are hundreds of examples of this in medicine. We have some understanding of autism pathophysiology, but need more research on this since there are very obvious aspects of autism pathophysiology that have not been studied. For example, a number of children with ASD have mitochondrial dysfunction markers. Most have immune dysfunction.Many have poor methylation status. All these are obviously linked in terms of the way the body functions, and understanding the links will ultimately provide us clues to treatment. How is it I cannot find a single study on a cohort of ASD children that has studied mitochondrial dysfunction markers AND immune status markers – not ONE SINGLE study in a peer-reviewed journal?

What are autism research $$ being spent on if we have failed to explore these basic questions?

2) WE NEED MORE TRIALS TREATING AUTISM PATHOPHSYIOLOGY WITH FDA-APPROVED MEDS: In areas where we do understand autism pathophysiology – or can at least make meaningful hypotheses around it – some pioneering phsycians have seen early success in treating with off-label applications of FDA-approved medications (e.g. Dr.Chez’s use of Namenda to address glutamate excitotoxicity in autism, which has been an amazingly successful intervention for my child). What we need is more trials of existing FDA-approved medications to treat the pathophysiology.

3) WE NEED TO REVISE THE DIAGNOSTIC STANDARD OF CARE IN NEUROLOGY, GI – An estimated 80% of children with autism have EEG abnormalities, only apparent through a 24-hour EEG. A significant percentage have mitochondrial dysfunction. And so on. Why has the *diagnostic* standard of care for autism in Child Neurology not been revised in 12 years? Are you advocating for this?

Similarly, many children with autism have GI disorders – these may well fit into standard syndromes like eosinophilic GI disorders or Crohn’s, but this has not been sufficiently explored since Pediatric GIs don’t seem to know how to handle GI disorders co-morbid with autism. In most cases, these are dismissed as “toddler diarrhea” and the parent is told that the child will grow out of it. Why is there not a diagnostic standard of care for autism in Pediatric Gastroenterology? Is this part of your advocacy agenda?

There is so much that you could be doing that substantially improves the lives of children who are already affected.

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